Pharmacological anticoagulation is the mainstay of treatment for patients with prothrombotic conditions. For over fifty years, the only oral anticoagulant available was warfarin, an inhibitor of the vitamin K epoxide reductase (VKOR) that recycles oxidized vitamin K. Warfarin has many drawbacks, including unpredictable pharmacokinetics that necessitate frequent monitoring of coagulation parameters and dose adjustment. However, in the event of emergency bleeding or the need for urgent surgery, antidotes exist that allow rapid and complete reversal.
Oral direct FXa inhibitors are emerging anticoagulants that have the potential to simplify dosing schemes and hemostatic monitoring in patients with prothrombotic diseases when compared to standard treatments, such as warfarin. Although these drugs have many advantages over warfarin, no fully efficacious reversal agent is available for these novel anticoagulants.
The lack of a specific countermeasure to their effects, however, is a critical unmet clinical need that could limit the widespread adoption of these agents due to fears of unmanageable bleeding.